title: Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.
abstract: We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Lucia
authors.initials: L
authors.lastname: Pirisi
authors.forename: Kim E
authors.initials: KE
authors.lastname: Creek
mesh_terms: D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000254:growth & development*; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry* / Q000821:virology*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000821:virology*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D053773:Transforming Growth Factor beta1; C060614:SKI protein, human
keywords: Cervical cancer; HPV16-mediated transformation; Human keratinocytes; Human papillomavirus; Ski; TGF-beta